Candidate: The candidate specifically came to UAB to pursue a longstanding career interest in epilepsy imaging research. His immediate goals are: 1) to establish routine use of multimodality image coregistration in the presurgical epilepsy evaluation at UAB, 2) to set up and establish the UAB Magnetic Source Imaging Laboratory for presurgical epilepsy and brain mapping evaluations, and 3) to complete manuscripts for publication from two ongoing projects at UAB and the University of California, San Francisco. This proposal is designed to address the candidates longterm career goals1) to produce research that elucidates the role and impact of developing and established functional imaging modalities in the presurgical evaluation, 2) to demonstrate the applicability of image coregistration to improve routine functional brain image interpretation, and 3) to design and test a completely noninvasive epilepsy localization algorithm that includes cortical brain mapping with functional imaging. Environment: UAB offers a unique combination of support, mentorship, and equipment resources to foster the candidate's career development. The Department of Neurology and The Epilepsy Center are both academically strong and economically sound. Dr. Kuzniecky (applicant's mentor) is a leading expert in the field of epilepsy imaging. Dr. George Howard (applicant's cosponsor) is Chairman of Biostatistics and an expert in clinical research design and biostatistical analysis. Uniquely available at UAB are all structural and functional epilepsy imaging modalities necessary for comparative studies. Research: Epilepsy surgery candidates without identifiable focal epileptogenic lesions on MRI present a particularly difficult problem. These patients who represent approximately 40% of the total epilepsy surgery population in the U.S. typically require expensive and invasive intracranial electroencephalography (ICEEG) to help localize the volume of brain tissue necessary and sufficient for the generation of seizures (epileptogenic zone). Functional epilepsy imaging tests offer the possibility to noninvasively identify abnormalities of brain function associated with the epileptogenic zone; however, the clinical role and prognostic value of these tests is not known. The main goal of this proposal is to gain descriptive information on the predictive and prognostic value of FDGPET, HMRSI, and MSI as compared to ICEEG and seizure control outcome from surgery. The primary hypothesis is that noninvasive functional imaging modalities, either alone or in combination with image coregistration, can predict localization of nonlesional partial epilepsy as indicated by ICEEG. The secondary hypothesis is that discordant imaging tests provide additional predictive information as indicated by surgical outcome. The specific aims are: (1) to determine the relative predictive value of FDGPET, HMRSI, and MSI (and various combinations of these tests using image coregistration) to replace or supplement the information provided by ICEEG, and (2) to determine the degree of image localization redundancy between functional imaging tests. Toward a longterm goal, it is expected that this study will provide the information needed to mount a welldesigned and efficient trial to evaluate the clinical impact of each of these functional imaging tests on the use of ICEEG and surgical outcome.